Navidea Biopharmaceuticals is developing [18F]NAV4694 as a diagnostic imaging agent that can be used to visualize beta-amyloid (A) plaques in the brains of living individuals. Alzheimer's disease is the leading cause of dementia. All patients with dementia caused by Alzheimer's disease have abundant A plaques in their brains. There is a great need to develop better means to identify individuals who are at high risk of developing dementia caused by Alzheimer's disease before their symptoms become severe. This need has arisen from the extensive efforts of many companies to develop new and better therapies for this dreaded disease. Ninety such candidate Alzheimer's therapies are currently under investigation. Due to the mechanisms of action of a large portion of these drug candidates, they are likely to be most effective when given to patients before they have significant dementia. The intent of these new therapies will be to prevent or delay the progression of their illnesses to frank dementia. The problem addressed by this proposal is how to best indentify these patients. A plaques begin to appear in the brains of Alzheimer's patients many years before they develop dementia. We recognize, as others, many individuals with A plaques never develop dementia. However, A plaques are indicative of Alzheimer's pathology, and once a patient with A plaques begins to experience cognitive decline, they are at high risk of progression to Alzheimer's dementia. When people with Alzheimer's pathology (i.e. A plaques) first experience cognitive symptoms, their symptoms are minimal. Such people are said to have Mild Cognitive Impairment (MCI). However, MCI can have many causes besides Alzheimer's pathology. Patients with MCI and the underlying pathology associated with Alzheimer's would be candidates for treatment with the new Alzheimer's disease modifying therapies currently under development, while MCI patients with other pathologies would not. In the proposed study, patients with MCI will be imaged with [18F]NAV4694 using positron emission tomography (PET) to identify those individuals with A plaques in their brains. All participants in the study will then be followed for at least 18 months to determine which individuals progress to frank Alzheimer's dementia. It is expected that all participants that progress to frank Alzheimer's dementia will have had evidence of A plaques that were visualized by [18F]NAV4694, while none of the participants lacking A plaques will have progressed to defined Alzheimer's dementia. Thereby, evidence will have been obtained indicating that [18F]NAV4694 imaging could be used to identify the portion of all MCI patients that is at high risk for developing Alzheimer's dementia. Other firms are also developing A imaging agents; however, Navidea Biopharmaceuticals believes, based on its recent clinical data directly contrasting [18F]NAV4694 vs. [18F]PIB, that the superior performance characteristics of [18F]NAV4694 compared to its competitors will make it the preferred imaging agent for this application.